My research directly addresses issues in protein structure prediction and de novo design of therapeutically useful molecules; this is part of a larger assault by the structural community on the protein folding problem. The resources of the Computer Graphics Laboratory (CGL) have proved invaluable in the comparative analysis and visualization of protein structures in the areas of molecular recognition of cytokines and receptors, and protein structure prediction by packing and symmetry considerations. Cytokine-receptor systems have emerged as a paradigm for molecular recognition due to intense structural efforts, both X-ray and NMR that have resulted in detailed 3D images of ligands in complex with modular receptors. As cytokines and their receptors fold in a small number of preferred conformations, it has proved useful to focus on the haemopoietic or blood cell system molecules for which there is a great amount of structural data available. We have been studying the structural determinants of binding in three determined complexes: growth hormone, interferon-gamma and tissue factor/factor 7.These insights will allow us to model accurately the analogous complexes of a myriad of other haemopoietic cytokines. In addition, it is well known that proteins are frequently composed of compact, globular and independently folding units called modules. 3D protein structures also frequently reveal the presence of internal fold symmetry which may be tied to the evolution of the fold from smaller module components; catalytic and/or binding sites are likely located at the interfaces of these modular domains. Fold prediction efforts are eased by the accurate detection of component module structures, and how these domains pack in three dimensions. In collaboration with Bob Fletterick, we have reviewed putative mechanisms for the construction of multidomain proteins; in concert with D. Gerloff and Fred Cohen, we have focused on the helical fold of an important class of cell cycle regulatory proteins.